Dataset Information

Comprehensive Genomic Profiling Identifies FAT1 as a Negative Regulator of EMT, CTCs, and Metastasis of Hepatocellular Carcinoma.

ABSTRACT:

Background

FAT atypical cadherin 1 (FAT1) acts as a tumor suppressor or oncogene, which regulates cell adherence, proliferation, motility, and actin kinetics. FAT1 gene expression is closely related to hepatocarcinogenesis; however, the function and mechanism of FAT1 in hepatocellular carcinoma (HCC) remain unclear.

Methods

Here, we screened for the FAT1, which is intimately linked to the development and progression of HCC, both in circulating tumor cells (CTCs) and tumor tissues using next generation sequencing (NGS). Immunohistochemical staining was performed to detect FAT1 protein expression. To determine the impact of FAT1 on epithelial-mesenchymal transition (EMT), migration and invasion of HCC, an in vitro transwell assay and Western blot were performed. Moreover, Gene Set Enrichment Analysis was carried out to discover the underlying mechanism. Finally, animal experiments were conducted to confirm the effects of FAT1 on HCC metastasis and tumorigenicity.

Results

Our results showed that FAT1 expression was decreased in HCC tissues, while in vitro and in vivo, the FAT1 knockdown facilitated invasion, cell motility, colony formation, and proliferation. FAT1 knockdown also resulted in decreased expression of E-cadherin and markedly elevated expression of N-cadherin, vimentin, and snail. We also confirmed our hypothesis from the analysis of group differences in the CTC phenotype and lung metastasis in nude mice.

Conclusion

Our findings illustrated that FAT1 played a negative regulatory role in the HCC EMT and metastasis, providing further evidence for the role played by FAT1 in the formation and progression of HCC.

SUBMITTER: Huang ZL

PROVIDER: S-EPMC10007982 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Comprehensive Genomic Profiling Identifies <i>FAT1</i> as a Negative Regulator of EMT, CTCs, and Metastasis of Hepatocellular Carcinoma.

Huang Zi-Li ZL Zhang Ping-Bao PB Zhang Jun-Tao JT Li Feng F Li Ting-Ting TT Huang Xiu-Yan XY

Journal of hepatocellular carcinoma 20230307

<h4>Background</h4>FAT atypical cadherin 1 (<i>FAT1</i>) acts as a tumor suppressor or oncogene, which regulates cell adherence, proliferation, motility, and actin kinetics. <i>FAT1</i> gene expression is closely related to hepatocarcinogenesis; however, the function and mechanism of <i>FAT1</i> in hepatocellular carcinoma (HCC) remain unclear.<h4>Methods</h4>Here, we screened for the <i>FAT1</i>, which is intimately linked to the development and progression of HCC, both in circulating tumor cel ...[more]

PMID: 36915393

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